The proposed research will define the mechanisms by which leukocytes such as granulocytes, macrophages and small lymphocytes accumulate at local inflammatory sites or areas of wounds. These mechanisms will be investigated in the following manner, using the method of Boyden to quantitate leukocyte chemotaxis in vitro. 1. Humoral effectors such as the complement, clotting and kinin systems will be studied to determine their role in mediating the accumulation of leukocytes, in conditions such as acute inflammation and wound healing. 2. In vitro and in vivo cellular immune reactions will be studied as a source of chemotactic factors for homologous leukocytes. The biochemical nature of the factors responsible for accumulation of inflammatory cells in cellular immune reactions in vivo will be determined. 3. In addition, the chemotactic ability of leukocytes from patients with increased susceptiblity to infections, and with inflammatory diseases such as rheumatoid arthritis, lupus erythematosus and periodontal disease will be evaluated. Attempts will be made to correlate defects in leukocyte chemotactic ability with disease expression.